Protein ion channels are nanometer‐scale pores that are central to many biological processes, including the sensing of a wide variety of molecules. They have also demonstrated potential for use in the sensitive and selective detection of ions, the characterization of polynucleotides and toxins as well as the screening of therapeutic agents against lethal anthrax proteins. Further advances in materials engineering, theory, and signal processing are needed to enable practical applications based on biological or synthetic nanopores.